The human thyrotropin (TSH) receptor has not previously been purified or characterized. This receptor is nor only important for its interaction with thyrotropin, but also for its interaction with thyroid-stimulating antibodies in Graves' Disease (a major cause of hyperthyroidism), as well as thyroid-blocking antibodies in idiopathic hypothyroidism. Using recombinant DNA methodology and monoclonal antibodies to the TSH receptor we have isolated several cDNA clones as well a 2 variant genes coding for a TSH receptor. This receptor shows specific binding to TSH as well as both stimulating and blocking antibodies. It has 7 membrane spanning domains analogous to several other polypeptide hormone receptors coupled to guanine nucleotide binding proteins. Enzymatic deglycosylation of TSH has been achieved by newly available endoglycosidase F preparations. The deglycosylated molecule shows decreased in vivo and in vitro bioactivity.